PMID- 23400546 OWN - NLM STAT- MEDLINE DCOM- 20130611 LR - 20211203 IS - 1097-0142 (Electronic) IS - 0008-543X (Linking) VI - 119 IP - 9 DP - 2013 May 1 TI - Identification of ROS1 rearrangement in gastric adenocarcinoma. PG - 1627-35 LID - 10.1002/cncr.27967 [doi] AB - BACKGROUND: Recently, chromosomal rearrangements involving receptor tyrosine kinases (RTKs) have been described in common epithelial malignancies, including nonsmall cell lung cancer (NSCLC), colorectal cancer, and breast cancer. One of these RTKs, c-ros oncogene 1, receptor tyrosine kinase (ROS1), has been identified as a driver mutation in NSCLC, because its inhibition by crizotinib, an anaplastic lymphoma receptor tyrosine kinase (ALK)/met proto-oncogene hepatocyte growth factor receptor (MET)/ROS1 inhibitor, led to significant tumor shrinkage in ROS1-rearranged NSCLC. Currently, only human epidermal growth factor 2 (HER2)-targeted therapy in combination with chemotherapy has been successful in significantly prolonging the survival of patients with advanced gastric cancer (GC). There is a need for the discovery of additional novel targets in GC. METHODS: Anti-ROS1 immunohistochemistry (IHC) was used to screen 495 GC samples and was followed by simultaneous ROS1 break-apart fluorescence in situ hybridization (FISH) and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses in IHC-positive samples. Fusion partners in ROS1-rearranged GC were determined by RT-PCR. In all 495 samples, HER2 amplification was identified with FISH, and MET expression was identified by IHC. RESULTS: Twenty-three tumor samples were ROS1 IHC-positive. Three of 23 patients were ROS1 FISH positive, HER2 FISH negative, and negative for MET overexpression; and 2 of those 3 patients harbored a solute carrier family 34 (sodium phosphate), member 2 (SLC34A2)-ROS1 fusion transcripts. No fusion partner was identified in the third patient. Both patients who had SLC34A2-ROS1 transcripts had poorly differentiated histology with recurrence and death within 2 years of curative surgery. ROS1 IHC-positive status was not identified as an independent prognostic factor for overall survival. CONCLUSIONS: In this study, an SLC34A2-ROS1 rearrangement was identified in GC, and the results provide a rationale for investigating the clinical efficacy of ROS1 inhibitors in this unique molecular subset of GC. Society. CI - Copyright (c) 2013 American Cancer Society. FAU - Lee, Jeeyun AU - Lee J AD - Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. FAU - Lee, Seung Eun AU - Lee SE FAU - Kang, So Young AU - Kang SY FAU - Do, In-Gu AU - Do IG FAU - Lee, Sujin AU - Lee S FAU - Ha, Sang Yun AU - Ha SY FAU - Cho, Jeonghee AU - Cho J FAU - Kang, Won Ki AU - Kang WK FAU - Jang, Jiryeon AU - Jang J FAU - Ou, Sai-Hong Ignatius AU - Ou SH FAU - Kim, Kyoung-Mee AU - Kim KM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130207 PL - United States TA - Cancer JT - Cancer JID - 0374236 RN - 0 (MAS1 protein, human) RN - 0 (Proto-Oncogene Mas) RN - 0 (Proto-Oncogene Proteins) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (ROS1 protein, human) SB - IM MH - Adenocarcinoma/*enzymology MH - Adult MH - Aged MH - Female MH - *Gene Rearrangement MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Male MH - Middle Aged MH - Protein-Tyrosine Kinases/*genetics MH - Proto-Oncogene Mas MH - Proto-Oncogene Proteins/*genetics MH - Reverse Transcriptase Polymerase Chain Reaction MH - Stomach Neoplasms/*enzymology EDAT- 2013/02/13 06:00 MHDA- 2013/06/12 06:00 CRDT- 2013/02/13 06:00 PHST- 2012/10/24 00:00 [received] PHST- 2012/11/21 00:00 [revised] PHST- 2012/11/27 00:00 [accepted] PHST- 2013/02/13 06:00 [entrez] PHST- 2013/02/13 06:00 [pubmed] PHST- 2013/06/12 06:00 [medline] AID - 10.1002/cncr.27967 [doi] PST - ppublish SO - Cancer. 2013 May 1;119(9):1627-35. doi: 10.1002/cncr.27967. Epub 2013 Feb 7.